Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000538027 | SCV000632858 | uncertain significance | Birt-Hogg-Dube syndrome | 2023-12-28 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 568 of the FLCN protein (p.Thr568Met). This variant is present in population databases (rs781733528, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with FLCN-related conditions. ClinVar contains an entry for this variant (Variation ID: 460606). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002413484 | SCV002715520 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-09 | criteria provided, single submitter | clinical testing | The p.T568M variant (also known as c.1703C>T), located in coding exon 11 of the FLCN gene, results from a C to T substitution at nucleotide position 1703. The threonine at codon 568 is replaced by methionine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV000538027 | SCV004195337 | uncertain significance | Birt-Hogg-Dube syndrome | 2023-07-21 | criteria provided, single submitter | clinical testing |